Psychiatric medications, science, marketing, psychiatry in general, and occasionally clinical psychology. Questioning the role of key opinion leaders and the use of "science" to promote commercial ends rather than the needs of people with mental health concerns.

Tuesday, March 10, 2009

The Primary Care Companion to the Journal of Clinical Psychiatry has a piece on Abilify for depression that illustrates many of psychiatry's woes. Full text of the article is here. The journal published an article titled "Examining the efficacy of adjunctive aripiprazole in major depressive disorder: A pooled analysis of two studies." The paper combines data from two previously published studies which examined the addition of Abilify to existing antidepressant treatment (1, 2). One of psychiatry's big-name academics, Michael Thase, signed on as lead author. I'm hoping that he didn't actually write the paper. Actually, there are eleven authors of the paper, which seems a little ridiculous given that the paper is an analysis of data which had already been collected for two previously published clinical trials. Seven of the authors are employees of Bristol-Myers Squibb (BMS) or Otsuka, which both market Abilify. Wait... If you look closely, you can see my favorite disclosure... In the fine print on the first page...

In case you can't read the fine print: In defense of Thase and the other academic authors, they may have not actually written any of the paper. Much or all of the writing appears to be creditable to Ogilvy Healthworld Medical Education. On their site, they note that they perform:

Clinical Development and Publications ManagementExperienced medical writers work closely with authors, editors and publishers to provide our clients with a full range of publishing options.

Whatever BMS/Otsuka paid you for this one simply was not enough. Why? Because whomever wrote this thing did an admirable job of focusing on the positive and completely ignoring the negative.

Erasing the Patient's Opinions: Remember, the article's title states that it examines the efficacy of adjunctive Abilify (adding Abilify to existing antidepressant treatment). So you'd think the article would mention all of the relevant depression data from the two relevant studies. Well, no. In the two stuides which are discussed in the article, patients were assessed on depression using the following measures:

Montgomery Asberg Depression Rating Scale (MADRS)

Inventory of Depressive Symptoms-Self Report Scale (IDS)

Quick Inventory of Depressive Symptoms Self-Report Scale (QIDS)

Using the MADRS, the authors conclude that adding Abilify to antidepressant treatment is more effective than adding placebo to antidepressant treatment. OK, fine, though it's not by a particularly huge margin. Mysteriously, the authors do not even mention that the self-report scales (IDS and its subscale, the QIDS) were used in the two trials. And why would they? In both trials, Abilify was not significantly better than placebo on these measures. A letter to the editor pointed out this glaring weakness in Abilify's claims of efficacy, the response to which was weak:

Noting that Abilify did not outperform placebo on the self-report measure in the trial, he wrote that "this may be due to the lower sensitivity" of the measure. So the drug wasn't the failure -- blame the rating scale instead. The people at BMS picked the scale and when it doesn't give results they like, then suddenly it's a poor measurement of depression. I bet Dr. Berman would not have complained about the instrument had it yielded results in favor of Abilify.

In the publications of each of the two clinical trials, the authors tried to downplay the fact that Abilify was no better than placebo according to patient self-reports. Then, when publishing an analysis that combined the results of the two trials, the authors go a step further by not even mentioning that patients completed a self-report. Right down the memory hole. In my opinion, any reasonable academic author writing about such research would want to note the strengths and limitations of Abilify in treating depression. The lack of benefit on patient-rated measures is a major weakness. Yet several big-time academics signed off on this paper despite its complete scrubbing of negative data. For that, I hereby nominate each author for a coveted Golden Goblet Award. And I credit the ghostwriter at Ogilvy with a fantastic job of serving his/her corporate clients. You, sir or ma'am, deserve kudos for a marketing job well-done.

The instructions for authors who submit to the Primary Care Companion to the Journal of Clinical Psychiatry state: "Conclusions should flow logically from the data presented, and methodological flaws and limitations should be acknowledged." Um, does completely scrubbing negative data count as failing to acknowledge limitations? I can see that the peer reviewers and/or editor really paid close attention to this paper.

Safety: The authors note that "adjunctive aripiprazole is relatively well-tolerated in patients with MDD." Relatively? Relative to what -- being hit with a baseball bat repeatedly? They note that akathisia occurred in 25% of patients on Abilify compared to 4% of patients on placebo. Restlessness: 12% vs. 2%; insomnia: 8% vs. 3%; fatigue: 8% vs. 4%; blurred vision: 6% vs 1%. The authors report that akathisia resolved in 52% of patients by the end of the study, which would also mean that for 48% of patients with akathisia, they were stuck with it at the end of the study. But don't worry, it's "relatively well-tolerated."

Overall, another example of a "research" publication being little more than a puff piece in favor of a drug. With big-name academics signed on as authors to add credibilty and just a fine print mention of a ghostwriter.

11 comments:

To state the obvious -- one has to wonder whether those few people who are responding to Abilify are not responding to it as an antidepressant but as a mood stabilizer or an antipsychotic and that reduction of those symptoms is not improving mood, as opposed to direct effects on mood.

How come academic psychiatrists like Michael Thase or Craig Nelson put their respected names on this biased, ghostwritten, recycled piece of sh*t?

Should we not expect academic authors to ensure that the article gives a balanced presentation of the risk-benefit profile of aripiprazole (Abilify)? Where is the frank discussion of akathisia in relation to emergent suicidality? Where is the frank discussion of weight gain? Where is the frank and numerate discussion of the long term risk of tardive dyskinesia? Where is the frank discussion of comparative efficacy for aripiprazole versus alternative augmenting agents? Where is a frank statement in the Abstract, where it might be noticed, that aripiprazole did not beat placebo in males or in Hispanic patients? That important information is buried in indirect allusions to “interactions.” Where is the discussion of duration of augmenting treatment with aripiprazole?

As an academic psychiatric professor, I used to admire Michael Thase's work. No more. This man is nothing but a Pharma Whore of the worst order -- he is the next winner of the Nemeroff Award for the most corrupted "academic" psychiatrist in play. My residents regard him in shame now.

It is nothing less than both amazing and pathetic how the pharma industry corrupts those who seem to have had a respectable history with colleagues prior to the money being shoved into these alleged KOL's pockets.

When in Rome,...Well, I didn't get trained in Rome. So for all who use the argument "everyone else is doing it", go fuck yourselves!!!

I really hope someone who admires or defends the behaviors of these jackasses reads this and gets pissed off. Now you know how I feel.

therapyfirst, board certified psychiatrist, and shamed physician of the whores and cowards I painfully must call colleagues.

I once tried to convince Dr. KOL to do the right thing. He “dressed me down” in front of my peers, but the final blow was brutal. “Some people should just stay home,” he declared.

Afterward I bawled my eyes out in Dr. Welby’s office. Dr. Welby cured me with words of wisdom: “Consuelo, we are not like him. Academics like him climb over the backs of others to get ahead. Now go back over there and tell him you will not be bullied!”

I know how hard a drug comes into practical uses, usually it takes about 7-10 years and undergoes very tough scientific research.I admit that there are sometimes new drugs don't have obvious effect on certain people, or certain time, but if totally deny it or say, it has totally no effect seems not that scientific...

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About Me

I'm an academic with a respectable amount of clinical experience and no drug industry funding. Given my lack of time, don't expect multiple daily updates. Certain things about clinical psychology, the drug industry, psychiatry, and academics drive me nuts, and you'll probably pick up on these pet peeves before long...